Six male, adult rhesus macaques (Macaca mulatta) were subjected to saline injections to establish baseline characteristics of cell-mediated immune functions. After the baseline characteristics had been established, morphine sulfate was administered to three of the six macaques at an initial (first week) dosage of 1 mg/kg morphine sulfate three times daily, followed by a morphine dosage of 3 mg/kg three times daily for the second week, and then 5 mg/kg three times daily for the third and subsequent weeks. After morphine dependency was established, all six macaques (three saline-treated and three morphine-treated) were each experimentally infected with 1 ml aliquot of simian immunodeficiency virus containing 1.58 x 103 dosage of SIVmac239. Thirteen months post-infection, AZT resistance emerged from autologous viruses isolated from morphine-treated macaques, but not from any of the control (saline-treated) macaques. Sequence analysis revealed altered reverse transcriptase gene from the SIV of morphine treated animals. *KEY*Rhesus monkeys, Morphine treatment, SIV, AZT, Mutations